Smart DNA Hydrogel-Responsive Encoding Enables Portable Nucleic Acid Detection

DNA hydrogels are promising materials for biosensing, but translating their molecular recognition capabilities into portable diagnostics is hindered by slow target diffusion, signal constraints, and bulk architecture. Here, we present a smart DNA hydrogel-responsive sensing platform termed Q-RAPID (Quick Response Analysis for Pathogen Identification Device) for portable nucleic acid detection. Q-RAPID integrates three functional modules. A paper-based module acts as a capillary-driven scaffold, miniaturizing the hydrogel matrix to accelerate target delivery and enhance molecular transport. A hydrogel sensing module spatially confines target-specific DNA hybridization, enabling programmable strand displacement that triggers a cascading colorimetric reaction for amplified visual output. A digital output module translates the colorimetric result into a smartphone-readable quick response (QR) code, allowing for automated classification and wireless reporting via integrated algorithms. In tests with a viral pseudovirus model and 100 clinical specimens, Q-RAPID identified target nucleic acids with 91% sensitivity, 97.3% precision, and 95% concordance were observed in the pseudovirus combination tests. The platform’s reconfigurable design allows detection of diverse respiratory pathogens and could broaden the reach of rapid molecular diagnostics in various healthcare settings, including resource-limited environments.